Mhc class i defect D81.6

Very rare (< 20 patients described worldwide), autosomal recessive mutations in the TAP1 - TAP2 or TAPBP gene(TAP = transporter associated with antigen processing), leading to defective HLA expression, and thus to a complex disorder of MHC-dominated antigen presentation or immune response (see also Immunodeficiencies/s.a. MHC class II defect).

The genes for the human HLA system are located on the short arm of chromosome 6 and the gene products play a central role in adaptive immunity with the presentation of peptides for their recognition by T cells. An intact MHC class I expression is also necessary for the physiological maturation of CD8-positive T cells. The gene products of TAP are integrated in the membrane of the endoplasmic reticulum (ER). They protrude into the cytosol with a transmembrane domain. These are relevant for both substrate and ATP binding. The TAP protein causes the transport of antigenic peptides from the cytosol into the endoplasmic reticulum. There they are coupled with MHC class I molecules and can be presented to the T-lymphocytes as MHC antigen complex. Pathogenetically, this disturbance leads to an incorrect processing of the antigen presentation.

Childhood, more rarely only in adulthood.

Recurrent bacterial infections of the upper and lower respiratory tract. In the late stage, these lead to destruction of the airways with bronchiectasis.

Granulomatous, even necrotizing lesions of the skin and airways occur in 50% of patients and resemble Wegener's disease in clinical expression. Patients with TAP-2 mutations usually have more severe disease than those with TAP1 mutations.

Symptomatically adapted to the infection situation.

1. Cerundolo V et al (2006) Description of HLA class I- and CD8-deficient patients: Insights into the function of cytotoxic T lymphocytes and NK cells in host defense. Semin Immunol 18: 330-336
2. de la Calle-Martin O et al (2001) Familial CD8 deficiency due to a mutation in the CD8 alpha gene. J Clin Invest 108: 117-123
3. Hauber I et al (1996) More on MHC class II deficiency. N Engl J Med 335: 977-978
4. Klein C et al (1993) Major Histocompatibility Complex class II deficiency - clinical manifestation, immunologic features and outcome. J Pediatr 123: 921-928
5. Reith W et al (2001) The bare lymphocyte syndrome and the regulation of MHC expression. Annu Rev Immunol 19: 331-373